The requirement of artemis in double-strand break repair depends on the type of DNA damage
The requirement of artemis in double-strand break repair depends on the type of DNA damage
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DOI：
10.1089/dna.2007.0649
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Adachi, Noritaka
中科院分区：
文献类型：
--
作者：
Kurosawa, Aya;Koyama, Hideki;Adachi, Noritaka
Artemis是最近发现的一种参与V（D）J重组和DNA双链断裂（DSB）修复的非同源末端连接（NHEJ）的因子。在这里，我们在人前B细胞系Nalm-6中进行了Artemis基因（ARTEMIS）的靶向破坏。出乎意料的是，我们发现缺乏Artemis的细胞对低剂量电离辐射的敏感性增加，但对高剂量电离辐射的敏感性没有增加。我们还表明，ARTEMIS缺陷的细胞是超敏的拓扑异构酶II抑制剂依托泊苷，但在更小的程度上比细胞缺乏DNA连接酶IV，NHEJ的关键组成部分。与DNA连接酶IV缺陷细胞不同，ARTEMIS缺陷细胞对ICRF-193不过敏，ICRF-193是一种拓扑异构酶II抑制剂，不稳定拓扑异构酶II-DNA可切割复合物。总的来说，我们的研究结果表明，Artemis只部分参与NHEJ途径修复人体细胞中的DSB。
Artemis is a recently identified factor involved in V(D)J recombination and nonhomologous end joining (NHEJ) of DNA double-strand break (DSB) repair. Here, we performed targeted disruption of the Artemis gene (ARTEMIS) in the human pre-B cell line Nalm-6. Unexpectedly, we found that cells lacking Artemis exhibit increased sensitivity to low doses, but not high doses, of ionizing radiation. We also show that ARTEMIS-deficient cells are hypersensitive to the topoisomerase II inhibitor etoposide, but to a much lesser extent than cells lacking DNA ligase IV, a critical component of NHEJ. Unlike DNA ligase IV-deficient cells, ARTEMIS-deficient cells were not hypersensitive to ICRF-193, a topoisomerase II inhibitor that does not stabilize topoisomerase II-DNA cleavable complexes. Collectively, our results suggest that Artemis only partially participates in the NHEJ pathway to repair DSBs in human somatic cells.
酵母中拓扑异构酶 I 和 RAD52 蛋白的差异表达揭示了双二氧代哌嗪化合物作用机制的新方面。
影响因子：
8.8
作者：
van Hille, B;Clerc, X;Creighton, A M;Hill, B T
通讯作者：
Hill, B T